The overall objective of this proposed study is to investigate in the healthy, antigen-sensitized and anaphylactic lungs the role and function of the autonomic nervous system, prostaglandins and cyclic nucleotides, both separately and with respect to their interactions. Specifically, we will continue to investigate the following: (1) the uptake and metabolism of catecholamines. Dose-response relationships and the effects of inhibitors and depletors will be studied in the whole perfused lung, lung fragments and isolated trachea/bronchi from guinea pig. (2) the sympathetic-parasympathetic nervous system pre-junctional balance. Modulation of sympathetic nerve stimulation release of NE by ACh and prostaglandins and, in turn, modification of parasympathetic nerve stimulation release of ACh by catecholamines and prostaglandins will be investigated in the perfused rabbit lung with isolated sympathetic chain with stellate ganglia and vagus nerves, a model system which was developed by us. (3) the effect of sympathetic and parasympathetic nerve stimulation on the release of prostaglandins and, conversely, modulation of the release of NE and ACh by protaglandins, using the rabbit lung model. (4) the conditions influencing prostaglandin release and its relationship to histamine release and the interactions between the mediators and the cyclic nucleotides. Thus, effects of divalent ions, temperature changes, exogenous prostaglandins and histamine and their antagonists; a detailed time course of the release of mediators and of the direction of cyclic AMP and GMP changes, and their interrelations; the influence on receptor sensitivity (as measured by adenylate cyclase activity and cyclic AMP accumulation) of adrenergic agonists and antagonists and of the autacoids and their blockers, will be studied in whole perfused lung and lung fragments from guinea pigs and isolated rat mast cells. Catecholamines and histamine are measured by fluorometric methods (Udenfriend and Crout, 1962 and 1973; Hakansson et al.1974); immunoreactive prostaglandins and cyclic nucleotides by RIA (Levine et al. 1971, Steiner et al. 1969 and 1972); and adenylate cyclase and phosphodiesterase activities according to Krishna et al. and Brooker et al, respectively (1968, 1968).